Is there an interaction between metaxalone and linezolid?

Potential Interaction Between Metaxalone and Linezolid

There is a potential risk of serotonin syndrome when metaxalone and linezolid are used concomitantly, and this combination should be avoided if possible.

Mechanism of Interaction

Linezolid is known to have monoamine oxidase inhibitor (MAOI) properties, though mild and nonselective, which can increase the risk of serotonin syndrome when combined with other serotonergic agents 1. While metaxalone is a skeletal muscle relaxant, its chemical structure and mechanism may contribute to serotonergic effects when combined with MAOIs like linezolid.

Risk of Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition that typically develops within 24-48 hours after combining serotonergic medications and presents with:

• Mental status changes: confusion, agitation, anxiety
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity
• Autonomic hyperactivity: hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea 2

Advanced symptoms can include fever, seizures, arrhythmias, and unconsciousness, which can be fatal if not promptly addressed 2.

Evidence and Clinical Implications

While there are no specific studies directly examining the interaction between metaxalone and linezolid, the American Academy of Child and Adolescent Psychiatry warns that linezolid plays a role in most cases of serotonin syndrome and should be avoided in combination with any other serotonergic drug 2.

Several case reports document serotonin syndrome occurring when linezolid is combined with other serotonergic medications:

• A case of probable serotonin syndrome with buspirone and linezolid 3
• Multiple cases with selective serotonin reuptake inhibitors (SSRIs) 4

Management Recommendations

If treatment with both medications is being considered:

1. First-line approach: Avoid the combination if possible and consider alternative antibiotics or muscle relaxants.

2. If linezolid is absolutely necessary:

   • Discontinue metaxalone before starting linezolid
   • Allow a washout period based on the half-life of metaxalone
   • Monitor closely for signs of serotonin syndrome
   • Use the lowest effective dose of linezolid
   • Limit duration of therapy 1

3. Alternative antibiotics to linezolid for gram-positive infections:

   • Vancomycin (for MRSA)
   • Daptomycin
   • Tigecycline
   • Quinupristin-dalfopristin 1

4. If serotonin syndrome develops:

   • Immediately discontinue both agents
   • Provide supportive care
   • Consider hospitalization for severe cases
   • Implement cooling measures for hyperthermia
   • Consider benzodiazepines for agitation and tremor 1

Monitoring Requirements

If the combination cannot be avoided:

• Monitor for early signs of serotonin syndrome, especially in the first 24-48 hours
• Regular assessment of vital signs, mental status, and neuromuscular function
• Weekly monitoring of complete blood counts if linezolid is used long-term 1

Conclusion

The combination of metaxalone and linezolid carries a potential risk of serotonin syndrome due to linezolid's MAOI properties. Healthcare providers should avoid this combination when possible or exercise extreme caution with close monitoring if the combination is deemed necessary.